RESEARCH DESIGN AND METHODS In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight
and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under
the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based
Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all
20 variants.

RESULTS When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant
increase in probability of being both overweight with an odds ratio of 2.00 (1.47–2.72), P = 4.0 × 10−5, and obese with an OR of 2.62 (1.76–3.92), P = 6.4 × 10−7, compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight
and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When
combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for
overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67).

CONCLUSIONS The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical
utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.

Footnotes

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